Salvianolic Acid B Alleviates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction by Restoring Epithelial Proliferation–Apoptosis Balance and Modulating the Gut Microbiota

Background: Intestinal epithelial barrier dysfunction, a major consequence of inflammatory and oxidative stress, contributes to enteric disorder progression. Salvianolic acid B (SAB), a prominent water-soluble phenolic compound in Salvia miltiorrhiza, shows intestinal protective potential, but the underlying mechanisms remain unclear. Methods: This study investigated the protective effects of SAB on intestinal barrier function using a lipopolysaccharide (LPS)-challenged piglet model and LPS-stimulated IPEC-J2 cells. Results: SAB alleviated LPS-induced intestinal injury, evidenced by reduced plasma diamine oxidase and D-lactate levels, improved intestinal morphology, decreased pro-inflammatory cytokines, and enhanced antioxidant capacity. SAB also strengthened intestinal barrier integrity by increasing goblet cell number and mucin 2 levels and upregulating tight junction protein expression. Moreover, SAB restored epithelial proliferation–apoptosis balance and increased PI3K/AKT/mTOR phosphorylation. Molecular docking and molecular dynamics simulations predicted a stable SAB–PI3Kα/p110α interaction, whereas LY294002 treatment attenuated SAB-mediated restoration of epithelial renewal and barrier integrity in LPS-treated IPEC-J2 cells. SAB also altered the jejunal microbial composition, including higher relative abundance of Streptococcus and lower relative abundance of Escherichia-Shigella, together with increased jejunal acetate and lactate concentrations. Conclusions: SAB alleviates inflammation-associated intestinal barrier dysfunction by restoring epithelial proliferation–apoptosis balance and regulating the microbiota–metabolite profile.